PHASE II STUDY WITH IODODOXORUBICIN IN MEASURABLE ADVANCED COLORECTAL ADENOCARCINOMA, EFFECTIVE RESCUE USING WEEKLY HIGH-DOSE 5-FLUOROURACIL (WFU)

AIMS AND BACKGROUND: To evaluate a new anthracycline 4'-iodo-4'-deoxydoxorubicin (I-DOX) in patients with measurable advanced colorectal adenocarcinoma in a phase II study. METHODS: We investigated therapeutic activity and toxicities associated with repeated courses of I-DOX 80 mg/m2 administered every 3 weeks. Eighteen patients entered the trial, all of them evaluable for response and toxicity. RESULTS: A total of 47 courses were administered. The median cumulative I-DOX dose was 238 mg/m2 (80-320). Myelosuppression, particularly leukopenia, was the most frequent and serious side effect associated with I-DOX treatment; World Health Organization (WHO) grade 3-4 leukopenia occurred in 4 patients (22%). No thrombocytopenia was observed except in 1 patient who presented WHO grade 4. Only 1 patient developed febrile neutropenia but recovered uneventfully. Overall, the I-DOX treatment was well tolerated. Grade 3-4 nausea/vomiting was observed in 2% of the cycles and no other severe toxicities were recorded. Echocardiography or multiple gated scan was performed before treatment and during follow-up in 14 patients to measure left ventricular ejection fraction (LVEF), and a decrease > 15% was detected in 3, including 1 whose LVEF fell below normal values (48%) (normal range > 49%). There were no cases of congestive heart failure or treatment-related deaths. No complete or partial response (PR) was observed. Twelve patients received weekly high-dose 5-fluorouracil (WFU) as rescue. Four patients had PR, 5 no change and 3 progressive disease (PD). The median time to PD of the whole group from study entry to failure after WFU was 30 weeks and the overall median survival was 11 months. CONCLUSIONS: As reported for other anthracyclines, I-DOX showed no activity in colorectal adenocarcinoma; however, the use of an investigational agent as front-line chemotherapy for colorectal adenocarcinoma does not compromise further response to 5-FU.